Exploring the Therapeutic Potential of Psilocybin: A Comprehensive Review of Clinical Trial Evidence and Implications for Rescheduling
Fatemeh Abolhasani, Hojjat Rezaiezadeh, Mohammad Amin Langarizadeh, Mehrdad Tavakoli, Mehran Ilaghi, Payman Zare, Faezeh Karbakhsh Ravari, Fatemeh Alamdar, Mohammad Banazadeh, Mohammad Shabani
Mini-Reviews in Medicinal Chemistry September 18, 2026 DOI: 10.2174/0113895575443239260828094859 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Key findings | The authors conclude that psilocybin, administered under structured psychotherapeutic supervision, shows therapeutic potential for several psychiatric conditions, with controlled trials indicating lasting improvements in mood, emotional well-being, and quality of life and generally mild, self-limiting side effects. They argue that further research is needed to optimize dosing protocols, assess long-term safety and effectiveness, and explore broader clinical applicability. |
Abstract
Psilocybin, a compound found in certain species of Psilocybe mushrooms, shows potential as a treatment for various psychiatric conditions. In the past decade, a growing body of evidence has shown the effectiveness of psilocybin in treating conditions, such as treatment-resistant depression, generalized anxiety disorder, post-traumatic stress disorder, and substance use disorders. This review provides a thorough overview of clinical and neurobiological studies investigating psilocybin's biological pathways and therapeutic outcomes. Psilocybin primarily acts as a serotonin 2A receptor agonist, modulating cortical and limbic networks involved in emotional regulation, neural plasticity, and cognitive flexibility. Controlled clinical trials have demonstrated that psilocybin, when administered under structured psychotherapeutic supervision, leads to significant changes in perception and self-awareness, resulting in lasting improvements in mood, emotional well-being, and overall quality of life. Reported side effects are generally mild and self-limiting, such as nausea, nervousness, and headaches, indicating a favorable safety profile. However, further research remains essential to optimize dosing protocols, assess long-term safety and effectiveness, and explore its broader clinical applicability. Additionally, if psilocybin were to be reclassified from a Schedule I substance, pending adequate regulatory approval and strong scientific evidence, it could represent a significant shift in psychiatric treatment, offering an innovative, mechanism-based therapeutic option for individuals who do not respond adequately to standard drug therapies.
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |